桑葉綠原酸藉由調控miR-34a控制脂肪堆積和發炎減少非酒精性脂肪肝

導致脂肪肝的原因有很多肥胖所占比例最高。非攝取酒精所引起的脂肪肝稱之非酒精性脂肪肝 n on alcoholic fatty liver disease NAFLD) 容易造成肝發炎 n onalcoholic steatohepatitis NASH)NASH)，甚至於纖維化 (Fibrosis) 而進一步發展成肝硬化 c irrhosis) 或肝癌 h epatocellular carcinoma) 。新綠原酸已被證實對於預防或治療糖尿病、高血脂症和冠狀動脈疾病都有成效，因此本篇欲進一步驗證新綠原酸對非酒精性脂肪肝之功效。本論文以細胞模式探討新綠原酸對於改善非酒精性脂肪肝的堆積和發炎的作用和機制，以油酸 o l eic acid) 誘導 H epG2 細胞的脂肪堆積結果證實新綠原酸確實能改善非酒精性脂肪肝的堆積和發炎的現象亦發現新綠原酸是透過 miR 34a 的減少導致 SIRT1 及 AMPK 的增加，而也發現 miR 34a 不是直接影響 AMPK ，是透過 SIRT1 去影響 AMPK ，進而調控促使脂質氧化酵素和轉錄因子，例如 PPAR α、 CPT1，增加脂質的 β 氧化作用並減少脂質合成酵素和轉錄因子，例如 :SREBP 1 、 SREBP 2 其中 SREBP 1 是和三酸甘油脂合成相關， SREBP 2 則和膽固醇合成相關，兩者達到降低非酒精性脂肪肝的堆積和發炎。本篇研究推論，新綠原酸最主要是透過調控 miR 34a ，導致脂肪 β 氧化相關蛋白表現增加 AMPK 和 PPARα 。進而減少脂質合成相關蛋白，透過減少 SREBP 1 和 FASN 的表現，降低三酸甘油脂合成，另外也透過表現，降低三酸甘油脂合成，另外也透過SREBPSREBP--22和和HMGHMG--CCoAoARR，，減少膽固醇的合成。另外也降低和肝臟發炎相關蛋白減少膽固醇的合成。另外也降低和肝臟發炎相關蛋白:NFkB和和TNFa，達到降低非酒精性脂肪肝的堆積和發炎之效果。研究結果顯示達到降低非酒精性脂肪肝的堆積和發炎之效果。研究結果顯示桑桑葉葉新綠原酸新綠原酸可可研發成為預防非酒精性脂肪肝的保健食品研發成為預防非酒精性脂肪肝的保健食品。。

關鍵字

新綠原酸；非酒精性脂肪肝

並列摘要

There are many reasons will causes fatty liver, and obesity is the most reason . Non alcoholic fatty liver disease (NAFLD) is caused by who don’t drink wines, the serious one will also cause liver inflammation(nonalcoholic steatohepatitis; NASH), fibrosis, cirrhosis and hepatocellular carcinoma. Neochlorogenic acid has been known to p revent or treat to diabetes, hyperlipidemia and coronary artery disease . I n this study, we intended to further confirm the efficacy of the neochlorogenic acid. In this study , we investigated the effect and mechanism of neochlorogenic acid to improv e the accumulation and inflammation of NAFLD in a cell model,and induce the accumulation of fatty liver in HepG2 cells by o leic acid. The results confirmed that the n eo chlorogenic acid can improve the fat accumulation and inflammation in NAFLD. Furtheremor e, we found that the n eo chlorogenic acid is via reduction of miR 34a to increase the proteins : SIRT1 and AMPK, but also know that miR 34a does not directly affect AMPK, is via SIRT1 to affect AMPK to regulat e the proteins of fat β oxidation such as: PP ARα, CPT 1 I n contrast to reduce the lipogenesis proteins such as: SREBP 1, SREBP 2 SREBP 1 r elated to the synthesis of triglyceride , and SREBP 2 is associated with cholesterol synthesis, both of which reduce the accumulation of NAFLD . The results show that mulberry neochlorogenic acid can be developed into a health ly food for preventing non alcoholic fatty liver.